Absorption of benzocaine -³H from semi-solid dosage forms following rectal administration in rats Public Deposited

http://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/jm214s25f

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  • The effect of concentration, vehicle and surfactant on the absorption of benzocaine -³H across the rat's rectal mucosa was investigated. Blood radioactivity levels were determined after the application of benzociane -³H containing suppositories and ointments. A wet oxidation method was used for sample digestion. Since the radioactivity counted is the sum of the total radioactive molecules of any chemical form, thin layer chromotography was used to separate benzocaine from its metabolites. The in vitro hydrolysis of benzocaine in blood and the in vivo hydrolysis of benzocaine was studied. The in vitro method did not show any hydrolysis of benzocaine. However, the in vivo study did show that hydrolysis takes place. Different concentrations of benzocaine -³H in the same suppository base gave different blood radioactivity levels. The radioactivity increased with an increase in benzocaine -³H concentration. The polyethylene glycol (PEG) suppository base containing benzocaine -³H gave radioactivity levels several times higher than the same amount of drug in a cocoa butter base. The incorporation of surfactants, Span 80 and Tween 80, into the PEG suppository dosage form did not affect the absorption of benzocaine significantly (p<. 05). The incorporation of Tween 80 into cocoa butter base significantly decreased the absorption of benzocaine (p<. 05). However, the incorporation of Span 80 into the cocoa butter suppository vehicle did not show any significant effect. The effect of five different ointment bases on the rectal absorption of benzocaine -³H were compared. The amount of absorption of benzocaine -³H was found to be in the following decreasing order: PEG>Neobase®> Aquaphor® :Water (1:1)> Aquaphor® and white petrolatum. The tissue distribution of benzocaine -³H was investigated. The radioactivity level of the organs studied increased along with the increase in blood radioactivity levels. The liver and kidney contained the highest levels of radioactivity. Methemoglobinemia was recently reported after the application of high concentrations of benzocaine containing suppositories. The effect of benzocaine on the degree of methemoglobin formation was investigated by the application of 20% benzocaine -³H H n Polyethylene glycol suppository and 20% benzocaine -³H Neobase ® Methemoglobinemia was observed after the application of 20% benzocaine -³H in Polyethylene glycol suppository. However, no methemoglobin could be measured after 20% benzocaine -³H in Neobase® was applied rectally.
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